• Title/Summary/Keyword: Dose optimization

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Optimization of Ferric Chloride Induced Carotid Artery Thrombosis Model in a Rat: Effect of Ginkgo biloba Extracts

  • Lee, In Sun;Choi, SeungGu;Jeon, Won Kyung
    • 대한임상검사과학회지
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    • 제43권4호
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    • pp.179-187
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    • 2011
  • Animal models are important tools in thrombosis research and preclinical drug development. In recent studies, ferric chloride ($FeCl_3$) has been widely used to induce arterial thrombosis in a variety of species. The purpose of this study was to find an optimal concentration of $FeCl_3$ and validate this model suited better for thrombosis research. A small piece of filter paper, soaked in $FeCl_3$ solution (10, 20 or 35%, v/v, in distilled water) was topically applied on the carotid artery of SD rats to measure the time to occlusion (TTO) and thrombus weight (TW) to ascertain 35%, as an optimal $FeCl_3$ concentration ($8.63{\pm}0.92min$; p =0.000, $0.79{\pm}0.03mg/mm$; p =0.000, respectively). To validate this experimental model, Ginkgo biloba special extract EGb761 (5, 10 or 30 mg/kg) as a reference agent administered by peritoneal route for 1h prior to the induction of thrombosis, showed significantly delayed TTO in a dose dependent manner ($18.50{\pm}2.17$, $29.17{\pm}1.83$, and $38.00{\pm}1.79min$, respectively) and significantly reduced TW and repaired collagen fibre in the injured vessel compare to vehicle group. Our results provide a simple, reproducible and well controlled in vivo screening system to induce thrombosis in rats by the topical application of 35% $FeCl_3$ to assess the efficacy of the new anti-thrombotic agents.

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Prediction of pharmacokinetics and drug-drug interaction potential using physiologically based pharmacokinetic (PBPK) modeling approach: A case study of caffeine and ciprofloxacin

  • Park, Min-Ho;Shin, Seok-Ho;Byeon, Jin-Ju;Lee, Gwan-Ho;Yu, Byung-Yong;Shin, Young G.
    • The Korean Journal of Physiology and Pharmacology
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    • 제21권1호
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    • pp.107-115
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    • 2017
  • Over the last decade, physiologically based pharmacokinetics (PBPK) application has been extended significantly not only to predicting preclinical/human PK but also to evaluating the drug-drug interaction (DDI) liability at the drug discovery or development stage. Herein, we describe a case study to illustrate the use of PBPK approach in predicting human PK as well as DDI using in silico, in vivo and in vitro derived parameters. This case was composed of five steps such as: simulation, verification, understanding of parameter sensitivity, optimization of the parameter and final evaluation. Caffeine and ciprofloxacin were used as tool compounds to demonstrate the "fit for purpose" application of PBPK modeling and simulation for this study. Compared to caffeine, the PBPK modeling for ciprofloxacin was challenging due to several factors including solubility, permeability, clearance and tissue distribution etc. Therefore, intensive parameter sensitivity analysis (PSA) was conducted to optimize the PBPK model for ciprofloxacin. Overall, the increase in $C_{max}$ of caffeine by ciprofloxacin was not significant. However, the increase in AUC was observed and was proportional to the administered dose of ciprofloxacin. The predicted DDI and PK results were comparable to observed clinical data published in the literatures. This approach would be helpful in identifying potential key factors that could lead to significant impact on PBPK modeling and simulation for challenging compounds.

The improvement effect of antioxidant activity of Aronia extract that fermented by Lactic acid bacteria isolated from the fermented seafoods

  • Choi, Ui-Lim;Lim, Jeong-Muk;Lee, Jeong-Ho;Moon, Kwang Hyun;Kim, Dae Geun;Jeong, Kyung Ok;Im, So Yeon;Oh, Byung-Taek
    • 한국자원식물학회:학술대회논문집
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    • 한국자원식물학회 2018년도 추계학술대회
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    • pp.110-110
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    • 2018
  • The purpose of this study was to evaluate the improved antioxidant activity of Aronia extract fermented by lactic acid bacteria isolated from fermented seafoods. Aronia fruits were collected from Sunchang, Chonbuk, South Korea. And these collected fruits were lyophilized for fermentation. For the selection of effective lactic acid bacteria useful for fermentation. Aronia fermented by lactic acid bacteria that isolated from fermented seafood was extracted with 60% ethanol. Antioxidant activity of Aronia extract was evaluated on the DPPH radical scavenging activity and total polyphenol contents were studied. To determine the optimal fermentation conditions, the changes of antioxidant efficacy was evaluated by controlling temperature (25, 30, 37, $40^{\circ}C$), Time (0~5 day) and inoculation dose of lactic acid bacteria (0.125~0.5ml). To confirm the antioxidative effect of Aronia fermented under optimal conditions, the DPPH & ABTS radical scavenging activity, total polyphenol & flavonoid contents were compared before and after fermentation were studied. 16 different kinds of lactic acid bacteria were isolated from fermented seafood, and of which antioxidant activity of Aronia fermented by Pediococcus pentosaceus B1 was maximum. Aronia fermentation at $37^{\circ}C$ was maximized when fermented for 3 days and fermentation time is decreased as the start inoculation amount of lactic acid bacteria increased. The degree of increase in antioxidant activity after Aronia fermentation is that DPPH & ABTS radical scavenging activity was increased about 27%, 20% and total polyphenols & flavonoids contents was increased about 12%, 15%. In the result of this experiment indicated that fermentation process enhances the antioxidant efficacy of Aronia.

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50nm급 불연속 나선형 패턴의 마스터 제작 (Fabrication of Master for a Spiral Pattern in the Order of 50nm)

  • 오승훈;최두선;제태진;정명영;유영은
    • 한국정밀공학회지
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    • 제25권4호
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    • pp.134-139
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    • 2008
  • A spirally arrayed nano-pattern is designed as a model pattern for the next generation optical storage media. The pattern consists off types of embossed rectangular dot, which are 50nm, 100nm, 150nm and 200nm in length and 50nm in width. The height of the dot is designed to be 50nm. The pitch of the spiral track of the pattern is 100nm. A ER(Electron resist) master for this pattern is fabricated by e-beam lithography process. The ER is first spin-coated to be 50nm thick on a Si wafer and then the model pattern is written on the coated ER layer by e-beam. After developing this pattern written wafer in the solution, a ER pattern master is fabricated. The most conventional e-beam machine can write patterns in orthogonal way, so we made our own pattern generator which can write the pattern in circular or spiral way. This program generates the patterns to be compatible with the e-beam machine from Raith(Raith 150). To fabricate 50nm pattern master precisely, a series of experiments were done including the design compensation for the pattern size, optimization of the dose, acceleration voltage, aperture size and developing. Through these experiments, we conclude that the higher accelerating voltages and smaller aperture size are better for mastering the nano pattern which is in order of 50nm. With the optimized e-beam lithography process, a spiral arrayed 50nm pattern master adopting PMMA resist was fabricated to have dimensional accuracy over 95% compared to the designed. Using this pattern master, a metal pattern stamp will be fabricated by Ni electro plating for injection molding of the patterned plastic substrate.

Effect of Cooking Method and Additives on the Freeze-Thaw Stability of Mung Bean Starch Paste for Preparation of Omija-eui

  • Han, Hyun-Jeong;Jang, Keum-Il;Bae, In-Young;Lee, Kwang-Yeon;Koo, Seung-Hyun;Kim, Mi-Kyung;Jun, Soo-Jin;Lee, Hyeon-Gyu
    • Food Science and Biotechnology
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    • 제18권5호
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    • pp.1230-1236
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    • 2009
  • Optimum conditions for the freeze-thaw stability (FTS) of mung bean starch (MBS) paste as a main ingredient in omija-eui were investigated. For the optimization of the paste preparation condition, the FTS of MBS prepared by boiling in a shaking water bath (BMSW) or by pressure-cooking in an autoclave (PCMA) were analyzed using a response surface methodology (RSM). In addition, the effects of various additives such as gums, sugars, and emulsifier were evaluated on the FTS of MBS paste prepared under optimal conditions. The predicted maximal FTS of MBS paste prepared by the PCMA method (73%) was higher than that of the paste prepared by the BMSW method (36%). In case of additives, gellan gum and sodium alginate effectively prevented the syneresis of MBS paste in the BMSW method and in the PCMA method, respectively. The use of a fructose fatty acid ester as an emulsifier decreased syneresis in a dose-dependent, while the addition of sugars accelerated syneresis. Consequently, MBS paste for omija-eui preparation may be efficiently prepared by adding sodium alginate and fructose fatty acid ester under the optimal conditions of 4.3% MBS content, $121^{\circ}C$ heating temperature, and $89^{\circ}C$ cooling temperature by pressure-cooking in an autoclave.

팬텀 영상을 이용한 PET 스캔시간의 최적화 연구 (Optimization of PET Scan Time Using Phantom Studies)

  • 정하규;김동현;정해조;손혜경;홍순일;윤미진;이종두;김희중
    • 한국의학물리학회지:의학물리
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    • 제13권3호
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    • pp.139-148
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    • 2002
  • The measured attenuation correction with transmission (Tx) scans produced quantitatively accurate images. However, it was not clear for optimal emission (Ex) and Tx scan time in PET imaging. This study was to evaluate acceptable Ex and Tx scan time by simulating clinical situations using various phantoms. Cylindrical and NEMA phantom were used for $^{18}$ F-PET scan using 2D protocol in GE Advance PETTM scanner. Cylindrical phantom was filled with 136 MBq 18F, and five regions of interests (ROI) were drawn on 23 slices. NEMA phantom had three inserts containing water, air and polytetrafluoro-ethylene (PTFE). Outside of these inserts were filled with 309 MBq of $^{18}$ F, and total 12 ROIs were drawn on 23 slices. Scans were carried out according to five Ex scan times: 2, 5, 10, 15, and 30 min, and nine Tx scan times: 2, 3, 4, 5, 7, 10, 15, 20, and 30 min. Images were reconstructed using measured attenuation correction, and ROI analyses were performed for all images, and mean, standard deviation (SD), coefficient of variation and percent errors were calculated. For cylindrical phantom study, ROI mean and SD were decreased as Ex and Tx time increased. Coefficients of variation were kept constant, when Tx was greater than 10 min. The amount of error decreased for the increment of Ex time from 10 min to 15 min was almost the same to that from 15 min to 30 min. In NEMA phantom Tx 15 min showed the lowest er개r level when the percent errors for three inserts were summed for all of the Ex times. This study suggested that Ex 15 min and Tx 15 min were acceptable as optimal scan time for the scanning protocol and the dose of radiopharmaceuticals used in these phantom study.

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주민보호조치를 위한 국내 방사선비상 개입준위 산출 (Derivation of Intervention levels for Protection of the Public in a Radiological Emergency in Korea)

  • 이종태;이관엽;강병위;오기훈;김창규
    • Journal of Radiation Protection and Research
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    • 제26권4호
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    • pp.357-365
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    • 2001
  • 정당성 및 최적화 개념이 도입된 비용-이득 접근법에 근거하여 우리나라의 방사선비상시 주민보호조치를 위한 개입준위 설정방법을 이론적으로 유도하였다. 부지특성자료인 각종 보호조치에 소요되는 비용과 선량회피로 얻어지는 금전적 값을 이용하여 옥내대피, 소개, 일시이주 및 영구정착에 대한 방사선 개입준위를 계산하였다. 그 결과 IAEA가 권고한 개입준위가 우리나라에서도 적용 가능함을 확인하였다. 아울러 의사결정에 참고할 수 있도록 최적화된 개입준위의 범위를 옥내대피 5 - 10 mSv/2일, 소개 25 -130 mSv/주, 일시이주 15 - 90 mSv/월 및 영구정착 600 - 3,500 mSv/평생 과 같이 제안하였다. 이 결과는 우리나라의 방사선 개입준위 기준에 대한 근거를 마련하고 기준치를 개선할 수 있는 자료로 활용될 수 있을 것으로 기대된다.

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Liquid chromatography-tandem mass spectrometric analysis of oleracone D and its application to pharmacokinetic study in mice

  • Lim, Dong Yu;Lee, Tae Yeon;Lee, Jaehyeok;Song, Im-Sook;Han, Young Taek;Choi, Min-Koo
    • 분석과학
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    • 제34권5호
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    • pp.193-201
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    • 2021
  • We have demonstrated a sensitive analytical method of measuring oleracone D in mouse plasma using a liquid chromatography-tandem mass spectrometry (LC-MS/MS). Oleracone D and oleracone F (internal standard) in mouse plasma samples were processed using a liquid-liquid extraction method with methyl tertbutyl ether, resulting in high and reproducible extraction recovery (80.19-82.49 %). No interfering peaks around the peak elution time of oleracone D and oleracone F were observed. The standard calibration curves for oleracone D ranged from 0.5 to 100 ng/mL and were linear with r2 of 0.992. The inter- and intra-day accuracy and precision and the stability fell within the acceptance criteria. The pharmacokinetics of oleracone D following intravenous and oral administration of oleracone D at doses of 5 mg/kg and 30 mg/kg, respectively, were investigated. When oleracone D was intravenously injected, it had first-order elimination kinetics with high clearance and volume of distribution values. The absolute oral bioavailability of this compound was calculated as 0.95 %, with multi-exponential kinetics. The low aqueous solubility and a high oral dose of oleracone D may explain the different elimination kinetics of oleracone D between intravenous and oral administration. Collectively, this newly developed sensitive LC-MS/MS method of oleracone D could be successfully utilized for investigating the pharmacokinetic properties of this compound and could be used in future studies for the lead optimization and biopharmaceutic investigation of oleracone D.

The Value of Computed Tomography Scan in Three-dimensional Planning and Intraoperative Navigation in Primary Total Hip Arthroplasty

  • Fabio Mancino;Andreas Fontalis;Ahmed Magan;Ricci Plastow;Fares S. Haddad
    • Hip & pelvis
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    • 제36권1호
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    • pp.26-36
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    • 2024
  • Total hip arthroplasty (THA) is a frequently performed procedure; the objective is restoration of native hip biomechanics and achieving functional range of motion (ROM) through precise positioning of the prosthetic components. Advanced three-dimensional (3D) imaging and computed tomography (CT)-based navigation are valuable tools in both the preoperative planning and intraoperative execution. The aim of this study is to provide a thorough overview on the applications of CT scans in both the preoperative and intraoperative settings of primary THA. Preoperative planning using CT-based 3D imaging enables greater accuracy in prediction of implant sizes, leading to enhancement of surgical workflow with optimization of implant inventory. Surgeons can perform a more thorough assessment of posterior and anterior acetabular wall coverage, acetabular osteophytes, anatomical landmarks, and thus achieve more functional implant positioning. Intraoperative CT-based navigation can facilitate precise execution of the preoperative plan, to attain optimal positioning of the prosthetic components to avoid impingement. Medial reaming can be minimized preserving native bone stock, which can enable restoration of femoral, acetabular, and combined offsets. In addition, it is associated with greater accuracy in leg length adjustment, a critical factor in patients' postoperative satisfaction. Despite the higher costs and radiation exposure, which currently limits its widespread adoption, it offers many benefits, and the increasing interest in robotic surgery has facilitated its integration into routine practice. Conducting additional research on ultra-low-dose CT scans and examining the potential for translation of 3D imaging into improved clinical outcomes will be necessary to warrant its expanded application.

영상유도 방사선 치료 시 CBCT에서 방사선 방호최적화를 위한 영상평가 (Image Evaluation for Optimization of Radiological Protection in CBCT during Image-Guided Radiation Therapy)

  • 최민호;김경완;이동연
    • 한국방사선학회논문지
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    • 제17권3호
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    • pp.305-314
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    • 2023
  • 의료기술의 발전과 방사선 치료 장비의 발전으로 세기변조방사선치료와 같은 고 정밀 방사선치료의 빈도수가 증가하였다. 정밀하고 복잡한 치료계획에서 방사선 치료 시 영상유도방사선치료는 필수가 되었다. 특히 선형가속기에 진단용 영상장비의 도입으로 CBCT스캔이 가능해졌으며 이는 3차원 이미지를 통해 환자의 자세를 검·교정할 수 있게 되었다. 보다 정밀한 환자 자세의 재현이 가능해졌지만, 영상획득과정에서 환자에게 전달되는 피폭선량은 무시할 수 없다. 방사선 치료분야에서 방사선 방호최적화는 필요하며 피폭저감화를 위한 노력은 필요하다. 하지만 3차원 CBCT영상 획득 시 피폭저감화를 위해 촬영조건을 변경하여 촬영할 경우 환자의 위치정렬을 할 수 없을 정도의 화질이나 인공물이 발생해서는 안 된다. 본 연구에서Rando phantom을 활용해 각 촬영조건별 영상을 스캔하고 평가하였다. 100 kV, 80 mA, 25 ms, F1 filter 180° 조건에서 가장 높은 SNR이 나타났다. 관전압, 관전류가 높아질수록 Noise가 감소했으며 보우타이필터는 높은 관전류에서 최적의 효과를 나타냈다. 실제 스캔된 이미지를 토대로 환자위치정렬이 모든 촬영조건에서 가능했으며 가장 낮은 SNR을 나타낸 70 kV, 10 mA, 20 ms, F0 filter 180° 조건에서 충분히 환자자세정렬을 위한 영상유도방사선치료는 가능함을 확인하였다. 본 연구에서 촬영조건에 따른 영상평가를 실시하였으며 피폭 저감화를 위해 낮은 관전압과 관전류, 작은 회전각 스캔이 선량 저감화에 효과적일 것으로 보인다. 이를 토대로 CBCT촬영 시 환자의 피폭선량을 가능한 낮게 해야 할 것이다.